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Monthly Archives: April 2014

Right now, hundreds of thousands of units of blood are in storage in blood banks across the country. But in terms of shelf life, they won’t last much longer than a gallon of orange juice.

Due to their short lifespan, the Red Cross requires for red blood cells to be used in 42 or fewer days after donation. In addition to a steady need for new or returning donors — the Red Cross relies on 9.2 million donors each year — this leads to the staggering costs associated with hosting nearly-constant blood drives.

But in recent months, researchers at the University of Rochester have been working on a way to use embryonic stem cells to generate red blood cells for clinical use.

James Palis, M.D.

James Palis, M.D., professor of pediatrics, hematology, and oncology in the Medical Center, and Rick Waugh, Ph.D., chair of the biomedical engineering department on River Campus, shared their research at an April seminar in Helen Wood Hall auditorium.

Problems of scale

A study from France that was published in the journal Blood in 2011 showed that red blood cells grown outside the body could be successfully infused back into a patient, and had lifespans on par with those of normal red blood cells.

“So there is a proof of principal that you can start with a source of progenitors, expand red cells and use them as a potential source of transfusion therapy,” said Palis.

Palis wanted to see if he could use embryonic stem cells and erythroid progenitors to generate self-renewing erythroblasts. After some successful preliminary results, Palis said that this type of red blood cell generation could be feasible on a larger scale.

However, each microliter (1/1,000,000th of a liter) of human blood contains 5 million red blood cells. This means that the average person has about 25 trillion red blood cells in their body at any one time.

Richard Waugh, Ph.D.

“So if, ultimately, this is going to serve as a source of blood, our biggest problem is one of scale,” said Palis. “Trying to synthesize that order of red cells is a mindboggling thought.”

Palis’s erythroblast cultures expand to a maximum concentration of about 2 million per 1 mL of media. This means that his cultures would need about 1,000 liters of media to generate just a single unit of blood.

“Clearly, that’s a crazy thought, so we said ‘It’s time for a bioengineer to help us figure out if it’s possible to grow more cells with less (media),” said Palis.

Significant challenges

Waugh stepped in, and worked with a team to create several bioreactor models that could fulfill this function.

Early attempts produced a decent number of cells, but a great majority of those cells had died in the process.

“So as you can see, there are some significant challenges when you try to go from standard culture dishes to something that can be operated without daily involvement of the technician, and without having to put together 1,000 units of media to produce a unit of blood,” said Waugh.

But Waugh said that the team has had some success using a new bioreactor that they’d recently developed. He didn’t give many details about it, saying that the team was planning to submit a patent on it, but one of Waugh’s students was able to use the bioreactor to grow red blood cells for three days, unattended, with 92 percent of the cells viable at the end of the process.

Waugh said that there is much work to be done, but he agreed with Palis that this method of red blood cell production could potentially be viable down the line.

“These self-renewing erythroblasts really show enormous promise for producing blood cells on a large scale,” said Waugh. “But we’re going to have to improve our bioreactors significantly if we’re going to get to the place where we’ll have some practical application.”

Though the “no texting at the dinner table” rule might provide a brief respite, it’s hard to find a teenager these days who doesn’t have his or her face buried in a smartphone.

And while the ubiquitous devices have created another frustration for parents everywhere who are trying to connect with their children, researchers at the University of Rochester are tapping into the near-universal form of communication in the hopes of increasing teenagers’ ability to manage their asthma — and keeping their parents posted about it.

Hyekyun Rhee, Ph.D.

Hyekyun Rhee, PhD, an associate professor of nursing and pediatrics in the Medical Center, and James Allen, PhD, professor of computer science, worked together to develop an interactive text messaging system to help teens manage their asthma.

They shared their research, which was recently published in the Journal of Patient Preference and Adherence, at an April seminar in Helen Wood Hall Auditorium.

Interactivity

Asthma affects approximately 1 in 10 children and teenagers, making it the most common chronic condition experienced by youths in the United States.

James Allen, Ph.D.

Additionally, research indicates that asthma flare-ups can often be prevented through early detection and management of symptoms and consistent use of preventive medication.

Text reminders have been used successfully to increase medication use and create better outcomes in previous adult studies, but a texting program has not been used for broader purposes, such as for symptom monitoring or promoting a partnership between parents and teens, said Rhee.

So she worked with Allen to develop a texting system — called the Mobile Phone-Based Asthma Self-Management Aid for Adolescents (mASMAA) — that could ask the teens a series of six open-ended questions and accurately interpret the responses.

For example, mASMAA could text a teen the question: “Did you take your asthma medication today?” Though ostensibly a “yes” or “no” question, mASMAA was capable of responding to a number of different return texts.

“Let’s say in this case, the patient says ‘Not yet,’” said Allen. “The system then does two things. First, it texts back ‘Let me know when you do,’ and then it sets a new alarm to ask again at 9 a.m. If 8 a.m. rolls around and the patient reports that they’ve taken the asthma med, it logs that, says ‘Thanks for letting me know,’ and overrides the alarm.”

The system was also programmed to identify a handful of words which it could record as symptoms and dozens more that it identified as medications. It also understood text lingo, such as “l8r” and “thx.”

Only when mASMAA received a text that indicated patient discomfort — or a text that was overly complicated — would the system alert a human coordinator, who could seamlessly take over the text conversation. And once mASMAA compiled its list of information for the day, it would send an email to the teen’s parents, summarizing information related to asthma (e.g., symptoms, activity levels, use of controller and controller meds) the teen had reported throughout the day.

So while a teen might give a dismissive “I’m fine,” when asked about their asthma, parents learned that in reality, their teen might actually have experienced some symptoms throughout the day which they sent and received texts about. With the extra information, the parents could help to manage their teens’ asthma more effectively.

“Teens want to take care of everything themselves, and asthma is no different,” said Rhee. “But the evidence suggests that parental involvement in care continues to be beneficial in reducing asthma-related incidents.”

Future improvements

After a group of teen patients and their parents used mASMAA in a two-week trial, the research team received a lot of positive feedback. Teens and parents both felt they had a greater sense of control over their asthma, and parents liked the daily reports so much that they asked if the system could start sending it to their teen’s pediatrician, as well.

With such strong user buy-in, a broad-scale implementation of a system such as mASMAA could lead to better patient outcomes and tremendous savings on preventable emergency room visits.

But a teen’s willingness to actually send texts back to the system is vital in making sure that mASMAA actually augments successful asthma management. So the research team also paid close attention to the suggestions they received in a post-study focus group.

Over the two week trial, teens responded to the six daily questions between 81 and 97 percent of the time, which Rhee said was a very good response rate. But in the focus group, the teens said that six daily questions was too many, and suggested that fewer questions would lead to even better response rates.

They also said that flexible timing on the texts would make for a more user-friendly experience. A 6 a.m. text makes sense on a school day, but on the weekend, that text was always waking them up.

Researchers also realized that they could continue to work to improve mASMAA’s vocabulary.

The CTSI Seminar Series for Spring 2014 continues on Tuesday, April 22nd with a presentation by two CTSI Year Out Trainees. The CTSI supports medical students interested in a year-out experience of mentored research in clinical or translational research. The following two trainees will be presenting their research:

The theme of the Spring 2014 series is “Crossing Elmwood: River Campus-Medical Center Research Collaborations” and will showcase ongoing research collaborations between the University research community and the Medical Center. The series also aims to stimulate new research teams and areas of investigation capitalizing on the existing strength of faculty and programs. The Organizing Committee for the series includes Robert Holloway, MD, MPH, Peter Lennie, PhD, Rob Clark, PhD, Stephen Dewhurst, PhD, Karl Kieburtz, MD, MPH, David Williams, PhD, Richard Waugh, PhD, and Joanna Olmsted, PhD.

The series takes place on Tuesdays from 12:15-1:15 pm in the Helen Wood Hall Auditorium. You can access the full schedule here. Lunch is provided. Please provide your own beverage. The University of Rochester School of Medicine and Dentistry designates this live educational activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

There are those who are quick to assert that African Americans are more likely to be overweight; that Hispanics are more likely to struggle with mental health issues. And when the data, on the surface, appears to match the stereotype, confirmation bias can make it an easy story to perpetuate.

Ann Dozier

But information collected in Monroe County over the past 17 years shows that researchers need to closely examine myriad contributing factors before declaring that race or ethnicity leads to an increased risk for certain behaviors or health conditions.

“We talk about racial disparities, but maybe there’s a lot more going on underneath that we need to be attentive to, rather than just labeling a difference due to race,” said Ann Dozier, RN, PhD, Associate Professor in Public Health Sciences.

Starting in 1997 and continuing in 2000, 2006, and 2012, the Monroe County Health Department began surveying a random sample of adults in Monroe County, and a deep dig into the results shows that over time a handful of factors are more strongly correlated than race or ethnicity when it comes to certain behaviors and health conditions.

Dozier, who spoke about the findings at a March seminar in Helen Wood Hall Auditorium, compared data from five of the categories: smoking, perceived health, mental health, obesity and overweight, and insurance coverage.

In addition to race or ethnicity, the data were adjusted for age, gender, education level, and whether the person was a city or suburban resident. Once controlling for these other conditions, race and ethnicity became almost a complete non-factor.

Smoking

Raw data showed that, at various points from 1997 and 2012, both African Americans and Hispanics were significantly more likely to be smokers than whites.

However, after adjusting for the four factors listed above, Black race and Hispanic ethnicity were not shown to be indicator for whether a person was a smoker in the 2006 and 2012 studies. (In 1997 and 2000, adjusted data showed that African Americans were actually less likely to be smokers than whites.)

Instead, significant indicators were age, education, and place of residence. Those below the age of 65, those with less education, and city-dwellers were all significantly more likely to be smokers.

Perceived health

Again, raw data showed that both African Americans and Hispanics, at various times between 1997 and 2012, were more likely to self-report their health as “fair” or “poor” than whites were.

But after adjusting for the four factors, no significant difference between self-reported perceived health was shown between Whites and African Americans in 2006 and 2012. African Americans did report worse perceived health at significant levels in 1997 and 2000.

Age, education, and place of residence were again seen as significant indicators. Those above the age of 65, those with less education, and city-dwellers were all significantly more likely to report a lower score for their perceived health.

Mental health

Participants were asked “Have you experienced stress, depression, or problems with emotion on 14 or more of the last 30 days?” Raw data showed that African Americans and Hispanics, at various times between 1997 and 2012, were more likely to answer “yes.”

After adjusting for the four factors, Black race and Hispanic ethnicity were rarely found to be significant indicators for poorer mental health. In 1997, Hispanics were still significantly more likely to report mental health stressors than whites, while in 2012, blacks were significantly less likely to report than whites.

Age and education were significant indicators for poorer mental health. Those below the age of 65 and those with less education were more likely to report mental health stressors.

Body Mass Index

BMI was broken into two groups: overweight and obese. Both raw data and adjusted data from the overweight group showed that minority groups were no more likely to be overweight than whites.

For obesity, adjusted data showed African Americans were more likely to be obese than whites in 1997, 2000, and 2006. By 2012, adjusted data showed no significant correlation.

Significant indicators were gender for the overweight group and education for the obese group. Men were more likely to be overweight, and those with less education were more likely to be obese.

Insurance Coverage

Once again, raw data showed that both African Americans and Hispanics, at various times between 1997 and 2012, were less likely to have health insurance than whites.

However, adjusted data showed no connection between Black race or Hispanic ethnicity and insurance coverage, except for at one point: in 2000, African Americans were less likely to have coverage.

Significant indicators were gender, age, and place of residence. Men, those below the age of 65, and city-dwellers were less likely to have health insurance.

Conclusions

Dozier said that the analyses did have some weaknesses. For one, all the data points are self-reported.

“So think about weight. Are people being honest about how heavy they are? That could actually be understated,” she said.

Researchers also weren’t able to adjust for other factors that might potentially contribute to these categories, such as marital status or income.

But conclusions can still be drawn from these findings. Less education is a factor in key health behaviors. Age is a factor in smoking, mental health reporting, and health insurance coverage. Men are more likely to be overweight and less likely to have insurance. And city-dwellers are more likely to smoke, and less likely to have insurance.

For each of these categories, race and ethnicity isn’t the end of the story.

“Disparities may have a component that may be attributable to race or ethnicity,” said Dozier. “But we should be cautious about overstating what that relationship is, and we should be looking at them in the context of potential confounding factors.”

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I would not have read the form, because I did not read any of the forms, because the forms are for lawyers, not for parents. I had not slept in days. I was scared out of my mind. I had the mental capacity of a drunk being chased by bears. What kind of form can protect a parent in a situation like that?

-Kelley Benham, Tampa Bay Times. October 18, 2013.

Dr. Carl D’Angio likes to share this passage because, well, the image of a drunk being chased by bears is so evocative.

Dr. Carl D’Angio

But he also shares it because the excerpt, written by a newspaper reporter whose daughter was born after just 23 weeks of gestation – barely halfway through pregnancy – highlights the often-colossal challenge faced by doctors and researchers looking to provide patients with an informed consent form that they will actually comprehend.

D’Angio, the host and first local presenter at the 2014 CTSI Symposium, shared a selection of research on the topic of informed consent. A neonatologist at UR Medicine’s Golisano Children’s Hospital, D’Angio included some of his own research, and showed that when it comes to providing truly informed consent, there are rarely any easy answers.

Contrasting findings

Prior to discussing his own findings, D’Angio touched on several seemingly conflicting studies that had been done in the past.

A commonly used approach to informed consent is to decrease the reading level of the forms as much as possible in the hopes of increasing understanding. But some studies have shown that decreasing the reading level isn’t always helpful, said D’Angio.

Lots of white space is good — consent forms should have about a third of the page be white space, said D’Angio. But an attractive form has its limits, as visual aids are sometimes helpful in increasing understanding, but not always.

Shorter consent forms have also been tested, including a study from the Journal of Pediatrics in 1998, which compared two consent forms. There was the traditional form, which was opt-in, and a shorter, modified consent form, which was opt-out; the modified form scored better when it came to understanding level. But a study published in 2007 in the same journal surveyed a group of parents of oncology patients about the informed consent process, and showed that a shorter form wasn’t always what they wanted.

“They wanted clearer information,” said D’Angio. “But many parents wanted more information rather than less. We know shorter forms may not always be practical, but they also may not always be preferred.”

D’Angio’s own studies have also generated inconclusive results when attempting to measure the benefits of a shorter form. In a randomized single-blind controlled study, his team tested the effectiveness of adding a simplified cover sheet to an informed consent form. The idea was to offer a short, easy-to-read summary of the study up front, while continuing to allow patients to read the entire form in more depth, if they wanted to learn more. But use of a cover sheet did not impact patients’ understanding.

Human interaction

Though many studies have led to inconclusive results, one of the only consistent findings across nearly every study that D’Angio mentioned was that human interaction increased understanding levels.

“Human interaction in the consent process is invaluable,” said D’Angio. “That came out over and over and over again.”

In a study that measured a consent form from the United Kingdom with one from the United States, both consent forms were understood more clearly when a verbal explanation was offered alongside.

And while his team’s study was inconclusive in terms of the addition of a cover sheet, D’Angio said that volunteers cited interaction, as well, as vital to their level of understanding.

“When asked about what was the most helpful part of the consent process, they said the interactions with faculty and staff were valued most highly,” he said.

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The 2014 CTSI Symposium, which took place on March 13, was titled “Ethics in Research: Consent Quandaries,” and was hosted by Dr. Carl T. D’Angio, Professor of Pediatrics and Medical Humanities & Bioethics at the School of Medicine and Dentistry. To view the Symposium in its entirety, click here.

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The CTSI Seminar Series for Spring 2014 continues on Tuesday, April 15th with a presentation by three CTSI Year Out Trainees. The CTSI supports medical students interested in a year-out experience of mentored research in clinical or translational research. The following three trainees will be presenting their research:

David Paul – “Using DTI to measure changes in occipital lobe white matter after decompression of the optic chiasm”

Jarrod Bogue – “Investigation of the fundamental biochemistry and conformational properties of a specific riboswitch from Neisseria gonorrhoeae”

The theme of the Spring 2014 series is “Crossing Elmwood: River Campus-Medical Center Research Collaborations” and will showcase ongoing research collaborations between the University research community and the Medical Center. The series also aims to stimulate new research teams and areas of investigation capitalizing on the existing strength of faculty and programs. The Organizing Committee for the series includes Robert Holloway, MD, MPH, Peter Lennie, PhD, Rob Clark, PhD, Stephen Dewhurst, PhD, Karl Kieburtz, MD, MPH, David Williams, PhD, Richard Waugh, PhD, and Joanna Olmsted, PhD.

The series takes place on Tuesdays from 12:15-1:15 pm in the Helen Wood Hall Auditorium. You can access the full schedule here. Lunch is provided. Please provide your own beverage. The University of Rochester School of Medicine and Dentistry designates this live educational activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.